| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10000599 |
| E.1.2 | Term | Acromegaly |
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| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part A:
To assess the efficacy of repeated s.c. injections at different doses of BIM 23A760 on growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in acromegalic patients after 6 months of treatment.
Part B:
To assess the long term safety of weekly injections of BIM 23A760 in patients with acromegaly. |
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| E.2.2 | Secondary objectives of the trial |
Part A:
•To assess the efficacy of repeated s.c. injection at different doses of BIM 23A760 on GH and IGF-1 levels in acromegalic patients after 3 months of treatment
•To assess the efficacy on finger circumference (ring size) of repeated s.c. injection at different doses of BIM 23A760
•To investigate the safety and tolerability of BIM 23A760 administered by repeated s.c. injection at different doses to acromegalic patients
•To investigate the pharmacokinetics of BIM 23A760 administered by repeated s.c. injection at different doses to acromegalic patients.
Part B:
• To assess the long term efficacy of weekly injections of BIM 23A760 in patients with acromegaly.
• To investigate the Cmin levels of BIM 23A760 after long term treatment. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Inclusion Criteria
All patients must fulfil the following:
1.The patient has provided written informed consent prior to any study related procedures.
2.The patient must have documentation supporting the diagnosis of acromegaly, including elevated GH and/or insulin-like growth factor-1 (IGF-1) levels.
3.Male or female, between 18 and 75 years of age inclusive.
4.Females of childbearing potential must provide a negative pregnancy test at the start of the study. Female patients who are at risk of becoming pregnant must agree to use an effective method of contraception such as double barrier contraception, an injectable or implanted hormonal contraceptive, combined oral contraceptive or an intra-uterine device (IUD). If a female patient is using a hormonal method of contraception then this must
be accompanied by the use of a second, nonhormonal method of contraception (e.g. condom).The patient must agree to use the contraception for two months after the last investigational medicinal product (IMP) administration. Nonchildbearing potential is defined as being postmenopausal for at least 1 year, or permanently sterilised at least 3 months before study entry.
5.Male patients must agree that, if their partner is at risk of becoming pregnant, they will use an effective method of contraception (see above).
6.The patient must have a serum level for IGF-1 ≥1.3 x ULN during the screening period (central laboratory results).
7.Nondiabetic patients must have a Nadir serum GH concentration ≥0.4 ng/mL in an oral glucose tolerance test (OGTT) during the screening period (central laboratory results).
8.If the patient is receiving replacement therapy (thyroid hormone, corticosteroid or sex hormone) the dose has been stable for at least one month prior to study entry.
9.If the patient is receiving treatment for hypertension, the dose has been stable for at least one month prior to study entry.
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| E.4 | Principal exclusion criteria |
Exclusion Criteria
Patients who have undergone pituitary surgery prior to study entry will be excluded if:
1.The time between pituitary surgery and study entry is less than 6 weeks.
2.After surgery, the patient has been treated with somatostatin (SST) analogues (except a single dose of immediate release formulation (IRF) octreotide for testing purposes performed at least 1 month before study entry), dopamine agonists (DAs) or GH receptor antagonists (GHRAs).
3.Before surgery, the patient has received >3 months’ treatment with SST analogues, DAs or GHRAs.
Patients who have not undergone pituitary surgery prior to study entry will be excluded from the study if:
4.The patient has received >3 months’ treatment with SST analogues, DAs or GHRAs.
5.The patient has received short acting SST analogues, DAs or GHRAs within 1 month of study entry.
In addition, patients will not be included in the study if:
6.The patient has received long acting SST analogues within 6 months of study entry.
7.The patient has undergone radiotherapy at any time prior to study entry.
8.It is anticipated that the patient will receive pituitary surgery or radiotherapy during the study.
9.The patient has received BIM 23A760 prior to the study.
10.The patient has uncontrolled diabetes (glycosylated haemoglobin (HbA1c)>8%).
11.The patient has insulin treated diabetes and has been treated for less than 6 months prior to study entry.
12.The patient suffers from macroadenoma with visual field defects due to chiasmatic compression.
13.The patient has had a previous cancer (except basocellular carcinoma of the skin and/or in situ carcinoma of
the cervix of the uterus).Patients with a history of cancer that was not basocellular carcinoma of the skin or in situ carcinoma of the cervix of the uterus can be included if they have been treated with curative intent and have been free from disease for more than 5 years.
14.The patient suffers from clinically severe cardiac valvular regurgitation, centrally assessed during the screening period.
15.The patient has any clinically significant hepatic abnormalities and/or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 x ULN during the screening period.
16.The patient has abnormal findings during the screening period, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient’s safety.
17.The patient has been treated with any other IMP prior to the first study visit without undergoing a washout period of 7 times the elimination half life of the IMP.
18.The patient has a known hypersensitivity to any of the test materials or related compounds and/or any known contraindications to magnetic resonance imaging (MRI).
19.The patient is likely to require treatment during the study with drugs that are not permitted by the study protocol.
20.The patient has a history of, or known current, problems with alcohol or drug abuse.
21.The patient has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an unco operative attitude.
22.Female patients are lactating or at risk of lactation during the study.
23.The patient is deprived of his/her freedom or rights by virtue of an order issued either by any judicial or administrative authorities, is unable to express his/her consent, or is commited to a social or health institution for reasons other than the study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy Endpoints
Part A:
• Proportion of patients with mean GH≤2.5 ng/mL and normalised IGF-1 at 6 months.
Part B
• Proportion of patients with IGF-1 ≤ ULN at each assessment timepoint
• Proportion of patients with GH≤2.5 ng/mL at each assessment timepoint
• Proportion of patients with GH≤2.5 ng/mL and normalised IGF-1 at each
assessment timepoint
• Quality of life, assessed using the EuroQoL EQ-5D questionnaire. |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 31 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study will be considered to have finished when the last patient has completed the last visit in the study. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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